Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r(g) = 0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking

Conflict about conflict

Purpose – There are a number of ongoing debates in the organizational literature about conflict in groups and teams. We investigate two "conflicts about conflict" (i.e., two meta-conflicts) in the literature: we examine whether and under what conditions conflict in workgroups might be beneficial and we also explore the idea that group members may not always perceive the same levels of conflict. Design/approach – We bring together the research and theorizing of the past 15 years to inform the current state of literature and move forward research on these conflicts about conflict. We examine and develop the two meta-conflicts to illustrate the importance of studying these ideas and to provide guidance for future research. Findings – These two meta-conflicts in the conflict literature are important to investigate as conflict is a multifaceted construct that contains many dimensions that may influence group outcomes. We explore these two issues by briefly reviewing the literature on conflict and then highlighting some of the recent research on the conflict debate (i.e., is conflict constructive or destructive?) and conflict asymmetry in workgroups. Originality/value – We identify interesting areas that future researchers could explore with respect to team conflict and conflict asymmetry

The Role of Prosodic Sensitivity in Children's Reading Development

While the critical importance of phonological awareness (segmental phonology) to reading ability is well established, the potential role of prosody (suprasegmental phonology) in reading development has only recently been explored. This study examined the relationship between children’s prosodic skills and reading ability. Hierarchical multiple regression analyses examined the unique contribution of word-level and phrase-level prosodic skills to the prediction of three concurrent measures of reading ability in 81 fourth-grade children (mean age 9;3 years). After controlling for phonological awareness and general rhythmic sensitivity, children’s prosodic skills predicted unique variation in word-reading accuracy and in reading comprehension. Phrase-level prosodic skills, assessed by means of an reiterative speech task, predicted unique variance in reading comprehension, after controlling for word reading accuracy, phonological awareness, and general rhythmic sensitivity. These results add to the growing body of evidence of the importance of prosodic skills in reading development

Brain fiber architecture, genetics, and intelligence: A high angular resolution diffusion imaging (HARDI) study

We developed an analysis pipeline enabling population studies of HARDI data, and applied it to map genetic influences on fiber architecture in 90 twin subjects. We applied tensor-driven 3D fluid registration to HARDI, resampling the spherical fiber orientation distribution functions (ODFs) in appropriate Riemannian manifolds, after ODF regularization and sharpening. Fitting structural equation models (SEM) from quantitative genetics, we evaluated genetic influences on the Jensen-Shannon divergence (JSD), a novel measure of fiber spatial coherence, and on the generalized fiber anisotropy (GFA; [1]) a measure of fiber integrity. With random-effects regression, we mapped regions where diffusion profiles were highly correlated with subjects' intelligence quotient (IQ). Fiber complexity was predominantly under genetic control, and higher in more highly anisotropic regions; the proportion of genetic versus environmental control varied spatially. Our methods show promise for discovering genes affecting fiber connectivity in the brain

An analysis of clustering of betapapillomavirus antibodies

Betapapillomaviruses (beta PVs) may contribute to the aetiology of cutaneous squamous cell carcinoma. However, no high-risk types have yet been identified, possibly because the high frequency of co-infection prevents a straightforward analysis of the independent effects of individual viruses. This study aimed to determine whether specific virus types were more likely to co-occur than others, thereby reducing the number of parameters needed in statistical models. Antibody data were analysed from controls who participated in case-control studies in The Netherlands, Italy and Australia and from participants in the German Nutrition Survey. Cluster analysis and two ordination techniques were used to identify patterns. Evidence of clustering was found only according to the number of viruses to which antibodies were detected. The lack of clustering of specific viral types identified suggests that if there are beta PV types that are independently related to skin carcinogenesis, they are unlikely to be identified using standard epidemiological methods.Molecular basis of virus replication, viral pathogenesis and antiviral strategie